16-2229631-CG-TA

Variant names:

• chr16-2229631-CG-TA
• NM_004424.5:c.371_372delCGinsTA
• E4F1 p.Ala124Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004424.5(E4F1):​c.371_372delCGinsTA​(p.Ala124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: E4F1 NM_004424.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

Genes affected

E4F1 (HGNC:3121): (E4F transcription factor 1) The zinc finger protein encoded by this gene is one of several cellular transcription factors whose DNA-binding activities are regulated through the action of adenovirus E1A. A 50-kDa amino-terminal product is generated from the full-length protein through proteolytic cleavage. The protein is differentially regulated by E1A-induced phosphorylation. The full-length gene product represses transcription from the E4 promoter in the absence of E1A, while the 50-kDa form acts as a transcriptional activator in its presence. Alternative splicing results in multiple transcripts encoding different proteins. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004424.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E4F1	NM_004424.5	MANE Select	c.371_372delCGinsTA	p.Ala124Val	missense	N/A	NP_004415.4	Q66K89
	E4F1	NM_001288776.2		c.371_372delCGinsTA	p.Ala124Val	missense	N/A	NP_001275705.2	H3BUJ7
	E4F1	NM_001288778.2		c.371_372delCGinsTA	p.Ala124Val	missense	N/A	NP_001275707.2	H3BSL4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E4F1	ENST00000301727.9	TSL:1 MANE Select	c.371_372delCGinsTA	p.Ala124Val	missense	N/A	ENSP00000301727.4	Q66K89
	E4F1	ENST00000564139.5	TSL:1	c.371_372delCGinsTA	p.Ala124Val	missense	N/A	ENSP00000457672.1	H3BUJ7
	E4F1	ENST00000565090.5	TSL:1	c.371_372delCGinsTA	p.Ala124Val	missense	N/A	ENSP00000456760.1	H3BSL4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-2279632;